Prevalence of Streptococcus pneumoniae and Staphylococcus aureus co-colonization in healthy children under five years: a systematic review

Nasal colonization is asymptomatic but facilitates transmission and can precede infection. Staphylococcus aureus and Streptococcus pneumoniae commonly colonize young children and contribute to substantial morbidity. Although pneumococcal conjugate vaccines (PCVs) have reduced vaccine-type (VT) carriage, serotype replacement and altered colonization patterns have emerged. This systematic review evaluated S. pneumoniae–S. aureus co-colonization in healthy children under five and the relationship between these colonization patterns. Following PRISMA guidelines and registered in PROSPERO (CRD42025632670), we systematically searched PubMed/Medline, EMBASE, Web of Science, and Google Scholar (February–March 2025) for studies reporting S.pneumoniae and S. aureus colonization in healthy children under five. Full-text English cross-sectional studies using nasal or nasopharyngeal samples and reporting colonization rates were included. Two reviewers independently performed study selection and data extraction. Study quality was assessed using the Joanna Briggs Institute (JBI) critical appraisal tools. Due to heterogeneity, meta-analysis was not performed. Nine cross-sectional studies (2002–2023) across eight countries involving 13,563 children were included; four were post-PCV and five were pre-PCV. Methodological quality was moderate to high. Nasopharyngeal swabs were most commonly used. Overall, 2,242 S. aureus and 5,417 S. pneumoniae isolates were identified. S. aureus colonization ranged from 5.6% to 56.0%, and S. pneumoniae from 14.1% to 94.0%. Co-colonization was reported in six studies, ranging from 2.0% to 24.1%. Predominant pneumococcal serotypes were 6B, 19 F, 23 F, 6 A, 11, and 23 A (pre-PCV) and 19 A, 6 C, 15B/C, and 11 A (post-PCV). Notably, post-PCV studies showed reduced pneumococcal carriage and increased S.aureus colonization, with an inverse association particularly for VT pneumococci. This review highlights global variation in S.aureus and S.pneumoniae colonization and co-colonization among healthy children under five. While some evidence suggests an inverse relationship and vaccine-related shifts, current evidence is insufficient to confirm the dynamics, determinants, or clinical significance of these interactions. Well-designed longitudinal studies with standardized methods are needed to clarify these relationships and guide surveillance, vaccination, and antimicrobial stewardship.